Intensified ocean exploration has revealed that high pressure causes severe tremors and EEG disturbances in divers working at great depths (the High Pressure Nervous Syndrome, HPNS). There is experimental evidence that general anesthetics may antagonize the effects of pressure and thus ameliorate at least some of the disabling symptoms of HPNS. At present, the cellular basis of neither HPNS nor of general anesthesia is known. The proposed study will examine the effects of pressure on the excitable cell properties of impulse initiation, conduction, and inhibitory as well as excitatory synaptic transmission, and will attempt to define the cellular site(s) of pressure-anesthetic interactions. Standard neurophysiological techniques of intra- and extracellular recording will be used in preparations selected for their adaptability to high pressure studies and for their well-defined physiological and pharmacological characteristics. Bioassay for stimulated acetylcholine release and acetylcholine iontophoresis will be used to isolate pre- and postsynaptic pressure effects. The proposed study will be the first systematic exploration of the effects of pressure on excitable cell functions. Preliminary results indicate that the effects of pressure at the cellular level are multiple and diverse. The characterization of pressure effects and of pressure-anesthetic interactions is expected to clarify the extent to which the use of anesthetics may be expected to antagonize the effects of pressure in deep dives. In addition, the identification of cellular sites of pressure-anesthetic antagonism may shed light on the cellular basis for anesthesia itself.